It's interesting that Ilya Bezprozvanny mentions the known interaction of TRP channels with PIP2. Di Pialo and colleagues report that Aβ disrupts PIP2 metabolism, which can be prevented in mice haploinsufficient for synaptonanin1 (1). This follows a study in which reduced PIP2 levels are reported in presenilin mutants (2). Several genes in the Down syndrome critical region have been reported to be involved in the expression synaptojanin 1, and reduced PIP2 expression is reported in the mouse model (4). TRPV1-expressing neurons in the spinal dorsal horn are reported to be glutamatergic (5). Xu and colleagues report that TRPV1 agonists capsaicin and resiniferatoxin facilitate LTP but suppress LTD (6). Soluble Aβ has been found to inhibit LTP and enhance LTD of glutamatergic transmission (7). Might we expect that altered TRPV1 function as a result of reduced PIP2 in AD may cause memory deficit? Might it also explain the taste deficit in AD (8,9)?

References:
1. PIP2 at the Core of Aβ Oligomers’ Synaptic Attack?

2. Beyond γ-Secretase: FAD Mutations Affect Calcium Channel via Lipid Messenger

3. Chang KT, Min KT. Upregulation of three Drosophila homologs of human chromosome 21 genes alters synaptic function: implications for Down syndrome. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17117-22. Abstract

4. Voronov SV, Frere SG, Giovedi S, Pollina EA, Borel C, Zhang H, Schmidt C, Akeson EC, Wenk MR, Cimasoni L, Arancio O, Davisson MT, Antonarakis SE, Gardiner K, De Camilli P, Di Paolo G. Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9415-20. Abstract

5. Zhou HY, Chen SR, Chen H, Pan HL. The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal horn. J Neurochem. 2009 Jan;108(1):305-18. Abstract

6. Li HB, Mao RR, Zhang JC, Yang Y, Cao J, Xu L. Antistress effect of TRPV1 channel on synaptic plasticity and spatial memory. Biol Psychiatry. 2008 Aug 15;64(4):286-92. Abstract

7. Ondrejcak T, Klyubin I, Hu NW, Barry AE, Cullen WK, Rowan MJ. Alzheimer's Disease Amyloid beta-Protein and Synaptic Function. Neuromolecular Med. 2009 Sep 16. Abstract

8. Lyall V, Phan TH, Ren Z, Mummalaneni S, Melone P, Mahavadi S, Murthy KS, Desimone JA. Regulation of the Putative TRPV1t Salt Taste Receptor by Phosphatidylinositol 4, 5-bisphosphate. J Neurophysiol. 2009 Dec 23. Abstract

9. Steinbach S, Hundt W, Vaitl A, Heinrich P, Förster S, Bürger K, Zahnert T. Taste in mild cognitive impairment and Alzheimer's disease. J Neurol. 2009 Sep 1. Abstract

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